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Published on: March 30, 2019
Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization
Steven J T Jackson1, Keith W Singletary, Richard C Venema
1Medical College of Georgia, Vascular Biology Center, CB 3330, 1459 Laney Walker Boulevard Augusta, GA 30912, USA.
Abstract:
Sulforaphane (SUL), an isothiocyanate derived from broccoli and other cruciferous vegetables, is known to induce phase II detoxification enzymes, disrupt cancer cell microtubule polymerization, and trigger cell cycle arrest in breast and colon cancer cells. Here, we provide the first evidence that SUL also acts to inhibit angiogenesis via suppression of endothelial cell proliferation. Bovine aortic endothelial (BAE) cells were exposed to concentrations of up to 15 microM SUL prior to cell cycle analysis and mitotic index quantification. Within 24 h, 15 microM SUL clearly induced G(2)/M accumulation and pre-metaphase arrest in BAE cells. Moreover, immunofluorescence tubulin staining indicated that this same SUL concentration was efficacious in not only disrupting mitotic progression, but also in perturbing normal polymerization of mitotic (and cytoplasmic) microtubules. Furthermore, daily administration of SUL (100 nmol/day, i.v. for 7 days) to female Balb/c mice bearing VEGF-impregnated Matrigel plugs strongly and significantly (P<0.05) suppressed angiogenesis progression as measured by hemoglobin concentration. Taken together, these findings suggest that the endothelial cell population is a novel target of SUL action both in vitro and in vivo. This mechanism of SUL-induced endothelial microtubule disruption and early mitotic arrest may further discern a potential role of SUL as a chemopreventive agent.
Insights
Sulforaphane (SUL), a compound from cruciferous vegetables, inhibits new blood vessel formation by disrupting endothelial cell growth and division. This suggests SUL may act as a chemopreventive agent by targeting angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sulforaphane (SUL) is a natural isothiocyanate found in cruciferous vegetables.
- SUL is known to induce phase II detoxification enzymes and disrupt microtubule polymerization in cancer cells.
- Previous studies indicate SUL triggers cell cycle arrest in breast and colon cancer cells.
Purpose of the Study:
- To investigate the effect of Sulforaphane (SUL) on angiogenesis.
- To determine if SUL suppresses endothelial cell proliferation.
- To explore the potential role of SUL as a chemopreventive agent.
Main Methods:
- Bovine aortic endothelial (BAE) cells were exposed to SUL (up to 15 microM) for cell cycle analysis and mitotic index quantification.
- Immunofluorescence tubulin staining was used to assess microtubule polymerization.
- In vivo studies involved daily SUL administration (100 nmol/day, i.v. for 7 days) to mice with VEGF-impregnated Matrigel plugs.
Main Results:
- SUL (15 microM) induced G(2)/M cell cycle accumulation and pre-metaphase arrest in BAE cells within 24 hours.
- SUL disrupted mitotic progression and perturbed microtubule polymerization in endothelial cells.
- In vivo, SUL significantly suppressed angiogenesis progression, as indicated by reduced hemoglobin concentration in Matrigel plugs.
Conclusions:
- Sulforaphane (SUL) inhibits angiogenesis by suppressing endothelial cell proliferation.
- SUL acts on endothelial cells both in vitro and in vivo.
- Endothelial microtubule disruption and mitotic arrest by SUL suggest its potential as a chemopreventive agent.
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